David J. Wheatley

Twenty year comparison of a Bjork-Shiley mechanical heart valve with porcine bioprostheses

Objective: To compare survival and outcome in patients receiving a mechanical or bioprosthetic heart valve prosthesis. Design: Randomised prospective trial. Setting: Tertiary cardiac centre. Patients: Between 1975 and 1979, patients were randomised to receive either a Bjork-Shiley or a porcine prostheses. The mitral valve was replaced in 261 patients, the aortic in 211, and both valves in 61 patients. Follow up now averages 20 years. Main outcome measures: Death, reoperation, bleeding, embolism, and endocarditis. Results: After 20 years there was no difference in survival (Bjork-Shiley v porcine prosthesis (mean (SEM)): 25.0 (2.7)% v 22.6 (2.7)%, log rank test p = 0.39). Reoperation for valve failure was undertaken in 91 patients with porcine prostheses and in 22 with Bjork-Shiley prostheses. An analysis combining death and reoperation as end points confirmed that Bjork-Shiley patients had improved survival with the original prosthesis intact (23.5 (2.6)% v 6.7 (1.6)%, log rank test p < 0.0001); this difference became apparent after 8–10 years in patients undergoing mitral valve replacement, and after 12–14 years in those undergoing aortic valve replacement. Major bleeding was more common in Bjork-Shiley patients (40.7 (5.4)% v 27.9 (8.4)% after 20 years, p = 0.008), but there was no significant difference in major embolism or endocarditis. Conclusions: Survival with an intact valve is better among patients with the Bjork-Shiley spherical tilting disc prosthesis than with a porcine prosthesis but there is an attendant increased risk of bleeding.

Respiratory dysfunction after uncomplicated cardiopulmonary bypass

Respiratory dysfunction is a well-recognized complication of cardiac operations. To quantify its current incidence and severity after uncomplicated cardiopulmonary bypass, serial measurements of arterial oxygen tension (PaO2), alveolar-arterial oxygen gradient (AaO2), and percentage pulmonary shunt fraction (%PSF) measured by a noninvasive technique were made in 129 patients (age, 59 +/- 8 years (mean +/- standard deviation) with good left ventricular function (left ventricular end-diastolic pressure < 15 mm Hg) undergoing isolated coronary artery operations (group 1) and 30 patients undergoing general surgical procedures (group 2). Measurements were made before operation and on the first, second, and sixth postoperative days. Seven patients in group 1 who required prolonged ventilation were excluded from further study. In group 1, between the preoperative and second postoperative days, there was a marked fall in PaO2 [89 +/- 11 versus 57 +/- 9 mm Hg; p < 0.001] and a marked increase in the AaO2 gradient [18 +/- 10 versus 50 +/- 11 mm Hg; p < 0.001)] and %PSF [3 +/- 1% versus 19 +/- 6%; p < 0.001)] with only modest improvement by the sixth postoperative day [PaO2, 67 +/- 11 mm Hg; AaO2, 45 +/- 11 mm Hg; %PSF, 15 +/- 4]. There were similar but less severe changes in PaO2 and AaO2 gradients in group 2 patients, with a return to baseline values by day 6.(ABSTRACT TRUNCATED AT 250 WORDS)

Polyurethane: material for the next generation of heart valve prostheses?

OBJECTIVES The prospects for a durable, athrombogenic, synthetic, flexible leaflet heart valve are enhanced by the recent availability of novel, biostable polyurethanes. As a forerunner to evaluation of such biostable valves, a prototype trileaflet polyurethane valve (utilising conventional material of known in vitro behaviour) was compared with mechanical and bioprosthetic valves for assessment of in vivo function, durability, thromboembolic potential and calcification. METHODS Polyurethane (PU), ATS bileaflet mechanical, and Carpentier-Edwards porcine (CE) valves were implanted in the mitral position of growing sheep. Counting of high-intensity transient signals (HITS) in the carotid arteries, echocardiographic assessment of valve function, and examination of blood smears for platelet aggregates were undertaken during the 6-month anticoagulant-free survival period. Valve structure and hydrodynamic performance were assessed following elective sacrifice. RESULTS Twenty-eight animals survived surgery (ten ATS; ten CE; eight PU). At 6 months the mechanical valve group (n=9) showed highest numbers of HITS (mean 40/h, P=0.01 cf. porcine valves), and platelet aggregates (mean 62.22/standard field), but no thromboembolism, and no structural or functional change. The bioprosthetic group (n=6) showed low HITS (1/h) and fewer aggregates (41.67, P=1.00, not significant), calcification and severe pannus overgrowth with progressive stenosis. The PU valves (n=8) showed a small degree of fibrin attachment to leaflet surfaces, no pannus overgrowth, little change in haemodynamic performance, low levels of HITS (5/h) and platelet aggregates (17.50, P<0.01 cf. mechanical valves, P=0.23 cf. porcine valves), and no evidence of thromboembolism. CONCLUSIONS In the absence of valve-related death and morbidity, and retention of good haemodynamic function, the PU valve was superior to the bioprosthesis; lower HITS and aggregate counts in the PU valve imply lower thrombogenicity compared with the mechanical valve. A biostable polyurethane valve could offer clinical advantage with the promise of improved durability (cf. bioprostheses) and low thrombogenicity (cf. mechanical valves).

New polyurethane heart valve prosthesis: design, manufacture and evaluation

In light of the thrombogenicity of mechanical valves and the limited durability of bioprosthetic valves, alternative designs and materials are being considered for prosthetic heart valves. A new tri-leaflet valve, made entirely from polyurethane, has been developed. The valve comprises three thin polyurethane leaflets (approximately 100 microns thick) suspended from the inside of a flexible polyurethane frame. The closed leaflet geometry is elliptical in the radial direction and hyperbolic in the circumferential direction. Valve leaflets are formed and integrated with their support frame in a single dip coating operation. The dipping process consistently gives rise to tolerably uniform leaflet thickness distributions. In hydrodynamic tests, the polyurethane valve exhibits pressure gradients similar to those for a bioprosthetic valve (St Jude Bioimplant), and levels of regurgitation and leakage are considerably less than those for either a bi-leaflet mechanical valve (St Jude Medical) or the bioprosthetic valve. Six out of six consecutively manufactured polyurethane valves have exceeded the equivalent of 10 years function without failure in accelerated fatigue tests. The only failure to date occurred after the equivalent of approximately 12 years cycling, and three valves have reached 527 million cycles (approximately 13 years equivalent). The simplicity of valve manufacture, combined with promising results from in vitro testing, indicate that further evaluation is warranted.

In vitro blood compatibility of surface-modified polyurethanes

Polyurethanes have proven durable materials for the manufacture of flexible trileaflet heart valves, during in vitro tests. The response of two polyurethanes of differing primary structure to parameters of blood compatibility has now been investigated, using an in vitro test cell. Platelet (beta-thromboglobulin) release, complement (C3a) activation, the activation of free plasma and surface-bound factor XII were studied using fresh, human blood (no anticoagulant) or citrated plasma in control and surface-modified polyurethane. Surface modifications were designed to affect material thrombogenicity and included covalent attachment of heparin, taurine, a platelet membrane glycoprotein fragment, polyethylene oxide (PEO), 3-aminopropyltriethoxysilane, and glucose or glucosamine. Unmodified control polyurethanes caused platelet release and complement activation. High molecular weight (2000 D) polyethylene oxide reduced platelet release slightly but only glucose attachment to the surface produced a significant reduction in platelet activation. All modifications reduced C3 activation compared with controls, but the greatest reduction was achieved with polyethylene oxide attachment or glycosylation. Most surface modifications were more activating of factor XII, both in plasma and on the material surfaces, than the control polyurethanes. Heparin and high molecular weight PEO produced the greatest activation of factor XII in the free plasma form, but low molecular weight PEO and glucosamine produced the greatest activation of surface-bound factor XIIa. The least activating surfaces, affecting both free plasma and surface-bound factor XIIa, were those treated with platelet membrane glycoprotein fragment and glucose. PEO surfaces performed relatively well, compared with controls and most surface modifications. The best overall surface, however, was the glucose-modified surface which was least activating considering all parameters of blood compatibility.

Assessment of changes in general health status using the short-form 36 questionnaire 1 year following coronary artery bypass grafting

OBJECTIVE The problem addressed in the study was to gain a greater understanding of the health benefits of coronary artery bypass grafting (CABG). The purpose of the study was to assess general health status, using the short-form (SF)-36 questionnaire, approximately 12 months following CABG, and to document any associations between pre-operative health status, level of social support, coronary artery disease (CAD) risk factors, CAD symptom severity and post-operative health status. METHODS The study was prospective and observational in design and included assessments at two time points, namely pre-operatively in a hospital outpatient department (1995-1996) and post-operatively at home (1996-1997). Two hundred and fourteen patients awaiting elective CABG were recruited a month before the expected date of operation. Pre-operative assessment included: (1), severity of symptoms; (2), CAD risk factors; (3), SF-36 questionnaire; and (4), social activities questionnaire. Post-operative assessment measured health status using the SF-36 instrument (mean, 16.4 months). Correlation and multiple linear regression analyses were used to identify factors associated with improved health status following CABG. RESULTS Two hundred and fourteen patients were assessed pre-operatively and underwent CABG. There was a 4.8% 30-day mortality rate, and 183 patients were followed for a mean of 16.4 months after CABG. SF-36 scores following CABG were improved across all of the eight domains (P<0.001). A higher social network score and higher pre-operative health status were associated with improved health status. Patients with lower health levels (SF-36 scores) prior to CABG were less likely to gain improvement in health (SF-36 scores) following CABG. Lower SF-36 scores following operation were influenced by the presence of diabetes mellitus, cigarette smoking, younger age, a high socio-economic deprivation category and higher alcohol intake. Many patients had uncorrected CAD risk factors at pre-operative assessment. CONCLUSIONS The SF-36 instrument was shown to be a useful and sensitive tool to assess differences and changes in the general health status of patients before and following CABG. High levels of social support were associated with improved health status post-operatively. Lower pre-operative general health status, the presence of diabetes mellitus and cigarette smoking were associated with poorer post-operative general health status.

Polyurethane heart valves: Fatigue failure, calcification, and polyurethane structure

Six flexible-leaflet prosthetic heart valves, fabricated from a polyetherurethaneurea (PEUE), underwent long-term fatigue and calcification testing. Three valves exceeded 800 million cycles without failure. Three valves failed at 775, 460, and 544 million cycles, respectively. Calcification was observed with and without associated failure in regions of high strain. Comparison with similar valves fabricated from a polyetherurethane (PEU) suggests that the PEU is likely to fail sooner as a valve leaflet. Localized calcification developed in PEUE leaflets at the primary failure site of PEU leaflets, close to the coaptation region of the three leaflets. The failure mode in PEU valves had the appearance of abrasion wear associated with calcification. High strains in the same area may render the PEUE leaflets vulnerable to calcification. Intrinsic calcification of this type, however, is a long-term phenomenon unlikely to cause early valve failure. Both polymers performed similarly during static in vitro and in vivo calcification testing and demonstrated a much lesser degree of calcification than bioprosthetic types of valve materials. Polyurethane valves can achieve the durabilities required of an implantable prosthetic valve, equaling the fatigue life of currently available bioprosthetic valves.

Differentiation between gaseous and formed embolic materials in vivo : application in prosthetic heart valve patients

Background and Purpose Doppler emboli detection is an established technique, but the nature of the underlying embolic material remains unclear. The intensity and spectral distribution of emboli signals could help to distinguish between signals arising from formed and gaseous emboli. We undertook this study to develop and evaluate a differentiation algorithm based on the spectral characteristics of emboli signals. Subsequently the algorithm was applied to patients with mechanical prosthetic cardiac valves. Methods Emboli signals detected in patients with carotid disease, acute stroke, and atrial fibrillation were used as formed emboli data, and signals detected in patients undergoing cardiac catheterization studies were used as gaseous emboli data. For each embolus signal, the maximal amplitude, the sum of amplitudes, and the spectral intensity distribution were calculated. Two hundred emboli signals from each category were used to develop a differentiation algorithm, which was subsequently evaluated on 501 additional solid and 995 gaseous emboli signals. The same algorithm was used to analyze 5958 emboli signals detected in 60 patients with mechanical prosthetic valves. Results The best results were obtained with an algorithm based on both the maximal amplitude and the sum of amplitudes (sensitivity, 99%; specificity, 96.5%). On subsequent evaluation, the sensitivity and specificity of the algorithm were 99.6% and 89.8%, respectively. Of the 5958 emboli signals detected in prosthetic valve patients, 92.4% were classified as gaseous. Conclusions Differentiation between gaseous and formed emboli signals, as detected by transcranial Doppler in vivo, is feasible by means of spectral analysis. Application of the differentiation algorithm in prosthetic valve patients suggests that the embolic material in these patients is gaseous. The possibility of distinguishing between different formed embolic materials with this technique remains to be evaluated.

Hydrodynamic function of polyurethane prosthetic heart valves: influences of Young's modulus and leaflet thickness.

The development of flexible polyurethane heart valves has been hindered by material degradation in vivo. Low modulus polyurethane leaflets are regarded as desirable to achieve good hydrodynamic function. However, low modulus materials may suffer high strain accumulation, hence poor durability. Higher modulus materials may improve durability, but may have poor hydrodynamic function. This study examines the hydrodynamic behaviour of biostable polyurethane valves, varying Youngs modulus from 5 to 63.6 MPa and mean leaflet thickness from 48-238 microm. Parameters studied included mean pressure gradient, energy losses and regurgitation over 5 equivalent cardiac outputs (3.6, 4.9, 6.4, 8.0 and 9.61 min(-1)) At low cardiac output, modulus was not significantly correlated with any parameter of valve opening. At 9.61 min(-1), modulus significantly influenced mean pressure gradient (p = 0.033). Mean leaflet thickness significantly correlated with mean pressure gradient and energy losses during forward flow at all cardiac outputs (p<0.001). This study demonstrates that, over a wide range of moduli, valve hydrodynamic function is not affected significantly by the material modulus. Leaflet thickness is a highly significant factor. Higher modulus elastomers in a range up to 32.5 MPa may be useful in prosthetic heart valve leaflet manufacture, retaining good hydrodynamic function while potentially extending the lifetime of the valve.

Endotoxemia, complement, and white blood cell activation in cardiac surgery: A randomized trial of laxatives and pulsatile perfusion

Endotoxin activates complement and white blood cells and all are implicated in the pathologic effects of cardiopulmonary bypass (CPB). We investigated if reduction in intestinal bacterial load with a laxative and/or pulsatile perfusion to improve bowel circulation during CPB reduced endotoxemia and complement and white blood cell activation. Sixty patients were randomized to four groups in a 2 x 2 factorial structure: group 1 (no laxative, nonpulsatile perfusion); group 2 (laxative, nonpulsatile perfusion); group 3 (no laxative, pulsatile perfusion); and group 4 (laxative, pulsatile perfusion). Plasma concentrations of endotoxin, C3a and C5a, and granulocyte elastase (GE) were measured before anesthesia, skin incision, and heparin administration; during CPB (1, 30, 60, 90, and 120 minutes and after protamine administration); and after CPB at 3, 6, 12, 24, and 48 hours and 7 days. In all groups there was a small increase in the concentration of endotoxin (overall from 6 ng/L before CPB to 11 ng/L at 90 to 120 minutes; p < 0.001) and significant increases in C3a, C5a, and GE levels but no significant differences among the groups. Endotoxin levels did not correlate with activation of complement or white blood cells. There was a weak correlation between duration of CPB and levels of C3a (r = 0.14; p < 0.03) and GE (r = 0.25; p = 0.001) but not endotoxin or C5a. There was a general correlation between levels of C3a and GE but not in individual patients. In conclusion, CPB results in statistically significant increases in endotoxin, C3a, C5a, and GE during CPB.(ABSTRACT TRUNCATED AT 250 WORDS)